ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1326T>A (p.Cys442Ter) (rs397508854)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570951 SCV000661067 pathogenic Hereditary cancer-predisposing syndrome 2017-08-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000256823 SCV000325014 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000256823 SCV000323300 pathogenic Breast-ovarian cancer, familial 1 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000481208 SCV000566455 pathogenic not provided 2015-04-30 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.1326T>A at the cDNA level and p.Cys442Ter (C442X) at the protein level. The substitution creates a nonsense variant, which changes a Cysteine to a premature stop codon (TGT>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as BRCA1 1445T>A using alternate nomenclature, has been reported in an individual with a family history of breast and/or ovarian cancer and an individual with multiple primary tumors diagnosed under the age of 60 (Kadouri 2004, Whitworth 2014). This variant is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000586087 SCV000698846 pathogenic Hereditary breast and ovarian cancer syndrome 2016-09-02 criteria provided, single submitter clinical testing Variant summary: The c.1326T>A (p.Cys442*) variant in BRCA1 gene is a nonsense change predicted cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay, which is a known disease mechanism in HBOC. The variant has been reported in several affected. This variant is absent from the large control population dataset of EXAC. Lastly, the variant has been classified as "pathogenic" by a reputable database/diagnostic center. Taken together, the variant was classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000481208 SCV000888842 pathogenic not provided 2018-01-05 criteria provided, single submitter clinical testing

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